1. Field of the Invention
The invention is in the field of materials and more particularly in the field of composite polymeric materials having suitable properties for medical and surgical applications.
2. Description of the Prior Art
Collagen, a major protein constituent of connective tissue in vertebrate and invertebrate animals, is widely used in medical and surgical applications in the fabrication of surgical sutures, blood vessel grafts, and in all forms of surgical prostheses. While collagen is better than most materials for such applications, it does have some significant deleterious properties.
One such property is the low resistance of collagen to resorption since it is a resorbable animal protein which is degraded by tissue enzymes (collagenases) present at implantation sites. Attempts have been made to solve this problem by crosslinking collagen, but these attempts have turned out to be only partially successful because rather high degrees of crosslinking are required to make collagen non-resorbable. Although crosslinking solves one problem, it creates another--that is, the tensile strength and other mechanical properties of collagen can suffer significantly when an excessively large degree of crosslinking is required to control the resorption to a very low level.
Other researchers have modified the properties of collagen by reacting it with other materials. Smith, in U.S. Pat. No. 3,527,225, describes resorbable surgical sutures formed from protein fibrils, such as collagen fibrils, which are oriented and crosslinked with up to 6% of polybasic polyacids, such as mucopolysaccharide acids. Smith also discloses that a very light treatment with formaldehyde or a very light chrome tanning improves the knot holding capability of these sutures without largely increasing resorption time.
Another deleterious property exhibited by collagen, insofar as its uses in surgical prostheses and other such applications are concerned, is that collagen, like most other polymeric materials, is non-compatible with blood. To qualify as blood-compatible, a material must not cause either platelet aggregation (white thrombus) or clotting of red cells (blood clot). Collagen causes both. Blood platelets are known to adhere to exposed collagen, such as occurs when blood vessels are mechanically injured, and this collagen-platelet interaction causes platelet aggregation. The detailed mechanistic aspects of this interaction have been extensively studied and reported in the literature. See, for example: Muggli, R. and Baumgartner, H. R., Thromb. Res., 3, 715 (1973); and Michaeli, D. and Orloff, K. G., Progress in Hemostasis and Thrombosis, T. H. Spaet, Ed., Gune and Stratton, N.Y., 3, 29 (1976). In addition, collagen has been implicated in acceleration of blood clotting by activation of Hageman factor (clotting factor XII). See Wilner, C. D., Nossel, H. L. and LeRoy, E. C., J. Clin. Invest., 47, 2608 (1968).
Previous efforts to synthesize blood compatible materials have centered largely around attempts to attach a blood-compatible material to the surface of a non-compatible material. The most successful materials were formed by attaching heparin, a known anticoagulant, to the surface of various synthetic polymers.
Attachment of heparin to such surfaces has been achieved by a variety of techniques, which are generally classifiable as either ionic interaction or chemical reaction. Both of these general techniques suffer from disadvantages, however. If the substrate surface is not completely covered, the uncovered portions which contact blood can cause formation of a thrombus or clot. Additionally, the possibility exists that, during the handling or use of such covered materials, the surface coating of heparin can become detached due to a mechanical incident or become hydrolyzed or otherwise be attacked chemically or biochemically by substances found in the blood or in vascular tissue; the resulting disruption of the surface coating is followed by exposure of underlying non-compatible substrate. Equally serious perhaps, is the difficulty that heparin occasionally desorbs from the substrate and migrates into the blood where, by virtue of its being a potent anticoagulant, heparin interferes strongly with the competence of healthy blood to clot, which is generally undesirable.